Al-Abdullah Ebtehal S, Al-Tuwaijri Hanaa M, Hassan Hanan M, Al-Alshaikh Monirah A, Habib Elsayed E, El-Emam Ali A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Molecules. 2015 May 6;20(5):8125-43. doi: 10.3390/molecules20058125.
The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a-e, 6, 7, 8a-c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a-g. The compounds 5a-e, 6, 7, 8a-c, 9, 10a, 10b, 14a, 14b and 15a-g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide.
异硫氰酸 1 - 金刚烷酯 4 与各种环状仲胺反应生成了相应的 N - (1 - 金刚烷基)硫代甲酰胺 5a - e、6、7、8a - c 和 9。类似地，4 与哌嗪以及反式 - 2,5 - 二甲基哌嗪以 2:1 的摩尔比反应，分别生成了相应的 N,N' - 双(1 - 金刚烷基)哌嗪 - 1,4 - 二硫代甲酰胺 10a 和 10b。N - (1 - 金刚烷基)-4 - 乙氧羰基哌啶 - 1 - 硫代甲酰胺 8c 与过量水合肼反应，除了生成少量副产物 4 - (1 - 金刚烷基)氨基硫脲 12 外，还生成了目标酰肼 11。酰肼 11 与异硫氰酸甲酯或苯酯反应，随后在氢氧化钠水溶液中加热，生成了 1,2,4 - 三唑类似物 14a 和 14b。酰肼 11 与各种芳香醛反应，生成了相应的 N' - 亚芳基氨基衍生物 15a - g。对化合物 5a - e、6、7、8a - c、9、10a、10b、14a、14b 和 15a - g 进行了体外抗某些致病性革兰氏阳性和革兰氏阴性细菌菌株以及类酵母真菌白色念珠菌的抗菌活性测试。化合物 5c、5d、5e、6、7、10a、10b、15a、15f 和 15g 对一种或多种测试微生物显示出强效抗菌活性。在链脲佐菌素(STZ)诱导的糖尿病大鼠中测定了化合物 5c、6、8b、9、14a 和 15b 的口服降糖活性。与格列齐特相比，化合物 5c 使血清葡萄糖水平显著降低。
